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Neutropenic Enterocolitis: Treatment & Medication
Updated: Jul 9, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
No published randomized control trials comparing conservative medical therapy with surgical intervention in neutropenic enterocolitis (typhlitis) exist; however, advocates for both types of therapy exist. The outcome appears to reflect the state of the underlying disease and other comorbidities at the time of clinical presentation rather than the treatment modality. Therefore, a uniform management strategy for neutropenic enterocolitis (typhlitis) cannot be recommended. Individualize the approach to each patient. Early recognition of neutropenic enterocolitis (typhlitis) in a patient who is neutropenic is paramount to a good outcome.
- Conservative management includes the following:
- Bowel rest and nasogastric suction
- Close monitoring of patients using serial abdominal examinations in an intensive care setting
- Intravenous fluids, blood, and platelet transfusions as necessary
- Parenteral broad-spectrum antibiotics: Antibiotics should include agents covering enteric gram-negative and anaerobic organisms, including Clostridium species. Metronidazole may also be considered if pseudomembranous colitis cannot immediately be excluded.
- Cultures: Obtain blood cultures for fungus, and consider early use of antifungal agents if the disease does not respond to antibiotics.22
- Avoidance of certain medications: Anticholinergic agents, antidiarrheal drugs, and narcotics may worsen the condition or further confuse the clinical picture of neutropenic enterocolitis (typhlitis).
Surgical Care
- Immediate surgery has been proposed by Shamberger et al in patients with neutropenic enterocolitis (typhlitis) and the following indications12 :
- Free intra-abdominal perforation
- Clinical deterioration during conservative medical therapy
- Differentiation from other acute abdominal conditions for which surgery is indicated
- Unrelenting intra-abdominal sepsis or abscess formation
- Continued hemorrhage with a platelet count and coagulation parameters within the reference range
- Tailor the surgical procedure to the operative findings.
- Choice of surgical procedures includes the following:
- Cecostomy and drainage
- A 2-stage right hemicolectomy or total abdominal colectomy, with or without a primary anastomosis
- Defunctioning of the colon with a loop ileostomy
- Normal-appearing serosal surfaces may conceal mucosal breakdown and necrosis. Therefore, resection should be extensive to assure removal of the diseased bowel.
- Consider elective right hemicolectomy in patients who have required repeated courses of chemotherapy and who have responded to initial conservative medical therapy. Recurrent episodes of neutropenic enterocolitis (typhlitis) have been reported in such patients.
Consultations
Joint management between medical and surgical teams is extremely important for a good outcome in patients with neutropenic enterocolitis (typhlitis).
Diet
Because the patient is fasting and on bowel rest, consider parenteral nutrition.
Activity
Patients with neutropenic enterocolitis (typhlitis) are usually extremely ill and in the intensive care setting on complete bed rest.
Medication
Because patients with neutropenic enterocolitis (typhlitis) have received numerous courses of antibiotics previously for other indications, a specific agent or regimen cannot be recommended, and the decision must be made on an individual basis. However, a few possible choices of antibiotics and antifungals are listed below. The author favors a combination of amikacin plus imipenem or cefepime/ceftazidime plus metronidazole in addition to vancomycin.
Consider adding antifungal agents if clinical improvement does not occur with antibiotics.
Antibiotics
Empiric broad-spectrum antibiotics are recommended to cover potential primary or secondary infectious causes of neutropenic enterocolitis (typhlitis) and to control sepsis. The antibiotics should cover aerobic and anaerobic enteric organisms, including Clostridium species, because anecdotal reports reveal an association between Clostridium septicum and neutropenic enterocolitis (typhlitis).
Metronidazole (Flagyl)
Synthetic antibacterial with good activity against gram-negative anaerobes, including Bacteroides species, and gram-positive anaerobes, including Clostridium species.
Adult
Loading dose for 70-kg adult: 15 mg/kg or 1 g IV over 1 h
Maintenance dose for 70-kg adult: 6 h following loading dose, infuse 7.5 mg/kg or 500 mg over 1 h q6-8h; not to exceed 4 g/d
Pediatric
Not established
Cimetidine may increase the toxicity of metronidazole; may increase the effects of anticoagulants; may increase the toxicity of lithium and phenytoin; disulfiramlike reaction may occur with orally ingested ethanol
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust the dose in hepatic disease; monitor for seizures and development of peripheral neuropathy; alcoholic beverages should be avoided, because a disulfiramlike reaction may occur and manifest as nausea, vomiting, abdominal cramps, headaches, and flushing; the IV form has to be diluted and neutralized before infusion because of low pH of reconstituted product
Cefepime (Maxipime)
Fourth-generation cephalosporin with good gram-negative coverage. Similar to third-generation cephalosporins but has better gram-positive coverage. Covers pseudomonads.
Adult
2 g IV q8h
Pediatric
<12 years: Not established
>12 years: Administer as in adults
At a high dose, probenecid decreases cefepime clearance; when used concurrently, aminoglycosides increasenephrotoxic potential of cefepime
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust the dose in patients with severe renal insufficiency; prolonged use of cefepime may predispose patients to superinfection
Ceftazidime (Ceptaz, Fortaz)
Semisynthetic, broad-spectrum, third-generation cephalosporin covering predominantly gram-negative aerobes, including pseudomonads. Provides poor coverage against gram-positive organisms and anaerobes.
Adult
2 g IV q8h
Pediatric
30-50 mg/kg/dose IV q8h; not to exceed 6 g/d
Nephrotoxicity may increase with aminoglycosides, furosemide, and ethacrynic acid; probenecid may increase ceftazidime levels
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust the dose in patients with renal impairment
Ceftriaxone (Rocephin)
Semisynthetic, broad-spectrum, third-generation cephalosporin covering gram-negative aerobes and anaerobes, including Bacteroides and Clostridium species. Not reliable for coverage against pseudomonads.
Adult
1-2 g IV qd or divided bid; not to exceed 4 g/d
Pediatric
50-75 mg/kg/d IV/IM divided q12h; not to exceed 2 g/d
Probenecid may increase levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust the dose in those with renal impairment; caution in women who are breastfeeding and in patients with an allergy to penicillin; reports of sonographic abnormalities in gallbladders of patients on this antibiotic exist, but clinical significance uncertain
Ticarcillin and clavulanate (Timentin)
Antipseudomonal penicillin plus beta-lactamase inhibitor that provides coverage against most gram-positive organisms, most gram-negative organisms, and most anaerobes.
Adult
3.1 g IV q4-6h
Pediatric
200-300 mg/kg/d IV divided q4-6h
Tetracyclines may decrease the effects of ticarcillin; high concentrations of ticarcillin may physically inactivate aminoglycosides if administered in the same IV line; effects when administered concurrently with aminoglycosides are synergistic; probenecid may increase penicillin levels
Documented hypersensitivity; treatment of severe pneumonia, bacteremia, pericarditis, emphysema, meningitis, or purulent or septic arthritis with oral penicillin during acute stage
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Perform CBCs before the initiation of therapy and at least weekly during therapy; monitor for liver function abnormalities by measuring AST and ALT during therapy; exercise caution in patients diagnosed with hepatic insufficiencies; perform urinalysis and BUN and creatinine determinations during therapy and adjust the dose if values become elevated; monitor blood levels to avoid possible neurotoxic reactions
Piperacillin and tazobactam (Zosyn)
Antipseudomonal penicillin plus beta-lactamase inhibitor. Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active multiplication.
Adult
3.375 g IV q6h
Pediatric
Not established
Tetracyclines may decrease effects; high concentrations may physically inactivate aminoglycosides if administered in the same IV line; effects when administered concurrently with aminoglycosides are synergistic; probenecid may increase penicillin levels
Documented hypersensitivity; treatment of severe pneumonia, bacteremia, pericarditis, emphysema, meningitis, or purulent or septic arthritis with an oral penicillin during the acute stage
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Perform CBCs before the initiation of therapy and at least weekly during therapy; monitor for liver function abnormalities by measuring AST and ALT during therapy; exercise caution in patients diagnosed with hepatic insufficiencies; perform urinalysis and BUN and creatinine determinations during therapy and adjust the dose if values become elevated; monitor blood levels to avoid possible neurotoxic reactions
Vancomycin (Vancocin, Lyphocin)
Tricyclic glycopeptide indicated for the treatment of suspected or confirmed serious infection with methicillin-resistant staphylococci, an entity not uncommonly observed in patients who are severely ill and in the intensive care setting.
To avoid toxicity, current recommendation is to assay vancomycin trough levels after third dose drawn 0.5 h before next dosing. Use creatinine clearance to adjust dose in patients diagnosed with renal impairment.
Adult
500 mg IV q6h or 1 g IV q12h
Pediatric
10 mg/kg IV q6h
Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; when taken concurrently with aminoglycosides, the risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in the presence of renal failure and neutropenia; red man syndrome is caused by IV infusion administered too rapidly (dose administered over a few min) but rarely happens when the dose is administered as 2-h administration or as PO or IP administration; red man syndrome is not an allergic reaction
Imipenem and cilastatin (Primaxin)
Potent broad-spectrum combination antibiotic consisting of a thienamycin class of antibiotic and cilastatin, which is an inhibitor of renal dipeptidase. Coverage includes gram-negative aerobes and anaerobes.
Adult
500 mg IV q6h
Pediatric
15-25 mg/kg/dose IV q6h
Coadministration with cyclosporine may increase the CNS adverse effects of both agents; coadministration with ganciclovir may result in generalized seizures
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Adjust the dose in patients with renal insufficiency; avoid use in children <12 y
Amikacin (Amikin)
For gram-negative bacterial coverage of infections resistant to gentamicin and tobramycin. Effective against Pseudomonas aeruginosa.
Irreversibly binds to 30S subunit of bacterial ribosomes. Blocks recognition step in protein synthesis and causes growth inhibition. Use the patient's IBW for dosage calculation.
Adult
7.5 mg/kg IV/IM q12h
Pediatric
Administer as in adults
Coadministration with other aminoglycosides, penicillins, cephalosporins, and amphotericin B increases nephrotoxicity; enhances the effects of neuromuscular blocking agents; causes respiratory depression; irreversible hearing loss may occur with the coadministration of loop diuretics
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Not intended for long-term therapy; caution in patients with renal failure (not on dialysis), hypocalcemia, myasthenia gravis, and conditions that depress neuromuscular transmission; aminoglycosides have the potential to cause tubular necrosis and renal failure, deafness due to cochlear toxicity, vertigo due to damage to the vestibular organs, and, rarely, neuromuscular blockade; the risk of nephrotoxicity is decreased by concomitant administration of antipseudomonal penicillin and once-daily dosing method; adjust the dose in the presence of renal impairment
Gentamicin (Garamycin)
Water-soluble aminoglycoside antibiotic with good coverage against gram-negative aerobes. Used in conjunction with other antibiotics for broad-spectrum coverage in intra-abdominal infections. Coadministration with carbenicillin or piperacillin provides synergistic effects against most strains of Pseudomonas aeruginosa. Follow each regimen by at least a trough level drawn on the third or fourth dose (0.5 h before dosing). May draw a peak level 0.5 h after 30-min infusion.
Adult
2 mg/kg IV loading dose, followed by 1.7 mg/kg IV q8h
Pediatric
2-2.5 mg/kg IV q8h
Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance the effects of neuromuscular blocking agents, prolonged respiratory depression may occur; coadministration with loop diuretics may increase the auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Documented hypersensitivity; nondialysis-dependent renal insufficiency
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Narrow therapeutic index (not intended for long-term therapy); caution in patients with renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust the dose in the presence of renal impairment; aminoglycosides have the potential to cause tubular necrosis and renal failure, deafness due to cochlear toxicity, vertigo due to damage to vestibular organs, and, rarely, neuromuscular blockade; the risk of nephrotoxicity is decreased by concomitant administration of antipseudomonal penicillin and once-daily dosing method
Tobramycin (Nebcin)
Used in skin, bone, and skin structure infections caused by Staphylococcus aureus, P aeruginosa, Proteus species, Escherichia coli, Klebsiella species, and Enterobacter species. Indicated in the treatment of staphylococcal infections when penicillin or potentially less toxic drugs are contraindicated and when bacterial susceptibility and clinical judgment justifies its use.
Adult
2 mg/kg IV loading dose, followed by 1.7 mg/kg IV q8h; to prevent increased toxicity caused by excessive blood levels, not to exceed 5 mg/kg/d unless serum levels are monitored
Pediatric
2-2.5 mg/kg IV q8h
Increases the effects of neuromuscular blockers and potentiates the effect of extended-spectrum penicillins; concurrent administration with amphotericin B, cephalosporins, and loop diuretics increases the risk of nephrotoxicity
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Avoid use in patients with renal impairment, preexisting auditory or vestibular impairment, or neuromuscular disorders; aminoglycosides are associated with nephrotoxicity and ototoxicity
Antifungal Agents
Consider adding antifungal agents if no clinical improvement occurs with broad-spectrum antibiotics. Amphotericin B is the preferred agent because non-albicans candidemia is more likely to be present and is usually fluconazole resistant. Consider liposomal amphotericin B if the infection is refractory to conventional amphotericin or in patients with renal failure.
Amphotericin B (Amphocil, Fungizone)
Produced by a strain of Streptomyces nodosus. Can be fungistatic or fungicidal. Binds to sterols, such as ergosterol, in the fungal cell membrane, causing intracellular components to leak, with subsequent fungal cell death.
Adult
Nonlipid amphotericin B: 0.3-1 mg/kg/d IV as single infusion
Liposomal amphotericin B: 1-5 mg/kg/d IV as single infusion
Pediatric
Administer as in adults
Antineoplastic agents may enhance potential for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; the risk of renal toxicity is increased with cyclosporine, azole antifungals, and skeletal muscle relaxants
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Monitor renal function, serum electrolytes (eg, magnesium, potassium), liver function, CBC, and hemoglobin concentrations; resume therapy at the lowest level (eg, 0.25 mg/kg) when therapy is interrupted for >7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in patients who are neutropenic and receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion); infusions can cause acute chills, fever, myalgia, anorexia, nausea, and, occasionally, hypotension, presumably due to the release of proinflammatory cytokines; febrile episodes cannot be prevented by premedicating with acetaminophen or diphenhydramine (responds to meperidine 25-50 mg IV)
More on Neutropenic Enterocolitis |
| Overview: Neutropenic Enterocolitis |
| Differential Diagnoses & Workup: Neutropenic Enterocolitis |
 Treatment & Medication: Neutropenic Enterocolitis |
| Follow-up: Neutropenic Enterocolitis |
| Multimedia: Neutropenic Enterocolitis |
| References |
| Further Reading |
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Further Reading
Related eMedicine Topics
- Colitis, Pseudomembranous [in the Radiology section]
- Necrotizing Enterocolitis [in the Radiology section]
- Necrotizing Enterocolitis, Surgical Treatment [in the Pediatrics: Surgery section]
- Neutropenia [in the Hematology section]
- Pseudomembranous Colitis [in the Infectious Disease section]
- Pseudomembranous Colitis, Surgical Treatment [in the General Surgery section]
- Typhlitis [in the Radiology section]
National Guideline Clearinghouse
- ACR Appropriateness Criteria® acute abdominal pain and fever or suspected abdominal abscess. American College of Radiology - Medical Specialty Society. 1996 (revised 2006). 7 pages. NGC:005138
- ASGE guideline: endoscopy in the diagnosis and treatment of inflammatory bowel disease. American Society for Gastrointestinal Endoscopy - Medical Specialty Society. 2006 Apr. 8 pages. NGC:004977
- Evidence-based care guideline for necrotizing enterocolitis (NEC) among very low birth weight infants. Cincinnati Children's Hospital Medical Center - Hospital/Medical Center. 2005 Jul 14 (revised 2007 Feb). 12 pages. NGC:005522
Keywords
neutropenic enterocolitis, typhlitis, necrotizing enterocolitis, ileocecal syndrome, pseudomembranous colitis, typhlitis, acute ileocecal enterocolitis, transmural inflammation of the small bowel and large bowel in myelosuppression and immunosuppression, profound neutropenia, cecum, ileum, ascending colon, cecitis, right lower quadrant pain
